CLV_PCSK_FUR_1

The subtilisin-like proprotein convertases are expressed extensively in mammalian neural and endocrine cells and play a major role in the proteolytic processing of both neuropeptide and peptide hormone precursors.

The members of the subtilisin-like family are proprotein convertases that process latent precursor proteins into their biologically active products. The prohormone-processing yeast KEX2 protease can act as an intracellular membrane protein or a soluble, secreted endopeptidase. The protein is required for processing of precursors of alpha-factor and killer toxin. PCSK1 (proprotein convertase 1, NEC1) and PCSK2 (proprotein convertase 2, NEC2) are type I proinsulin-processing enzymes that play a key role in regulating insulin biosynthesis. They are also known to cleave proopiomelanocortin, prorenin, proenkephalin, prodynorphin, prosomatostatin and progastrin. PACE4 (paired basic amino acid cleaving system 4, SPC4) is a calcium-dependent serine endoprotease that can cleave precursor protein at their paired basic amino acid processing sites. Its substrates include transforming growth factor beta-related proteins, proalbumin, and von Willebrand factor. Furin (PACE, paired basic amino acid cleaving enzyme, membrane associated receptor protein) is serine endoprotease responsible for processing a variety of substrates (proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor). PC7 (proprotein convertase subtilisin/kexin type 7) is closely related to PACE and PACE4. This calcium-dependent serine endoprotease is concentrated in the trans-Golgi network, associated with membranes, and is not secreted. It can process proalbumin. PC7 and furin are also thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140.